An approach to the development of long-acting opiate antagonists is described. Such agents would be useful for pharmacologic and chemical characterization of opiate receptors and could be of potential value in the prophylactic treatment of opiate addiction. Naloxone, a potent opiate antagonist, will be modified at the C-6 position with reactive substituents of varying length and orientation in an effort to uncover compounds that selectively alkylate opiate antagonist receports. The target compounds will be tested in mice, guinea pig ileum, and rat-brain tissue. The specificity of the action of the target compounds will be evaluated by receptor protection experiments.